Hormonal
Central exposure to palmitic acid (a saturated fatty acid) induces hypothalamic insulin resistance by triggering the translocation and activation of the PKC-θ isoform, whereas oleic acid (a monounsaturated fatty acid) does not.
In the brain, saturated fats (specifically palmitic acid) disrupt insulin signaling by activating a specific enzyme (PKC-θ), leading to resistance. Monounsaturated fats (oleic acid) do not cause this disruption. This suggests that the type of fat matters significantly for brain metabolic health, not just the total amount.
CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-θ to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-θ nor induced insulin resistance.
Why this rating
Strong mechanistic evidence in rodents using multiple methods (in vivo, in vitro, knockdown), but lacks human clinical data.
Source
Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents
Stephen C. Benoit et al. · Journal of Clinical Investigation · 2009
DOI 10.1172/jci36714
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